Description:
Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

Description:
Because the many physicians and students of heredity have not been closely associated in finding that the causes of cardiovascular diseases might lie, in a large measure, to an inherited predisposition, this study has been undertaken; first, to contribute to several more case studies of cardiovascular diseases to the knowledge of heredity; second, to find if there is a possible successive occurrence of cardiovascular diseases in generation after generation; and third, to determine a possible mode of transmission from parents to offspring by an analysis of nine genealogies.

Description:
Coronary heart disease leads to myocardial infarction and is a major cause of death in the US. Myocardial infarctions result from atherosclerotic plaque deposits in the coronary arteries, reducing blood flow through these arteries which supply oxygen and nutrients to the heart muscle. The two major approaches for restoring adequate blood flow are coronary bypass graft surgery and coronary angioplasty. Angioplasty is a routinely used clinical procedure, where a deflated balloon attached to the end of a long catheter is inserted into an artery in the leg and then advanced through the aorta into the blocked regions of the coronary arteries. After positioning in the occluded region of the artery, the balloon is inflated with a pressurized saline solution which opens the artery restoring blood flow by pressing the atherosclerotic plaque into the vessel wall. Angioplasty is a widely performed procedure with the coronary arteries and is a much less expensive alternative to coronary bypass surgery. The best patients for angioplasty are those with single occlusions and this method is preferred over bypass grafting because of the significantly reduced expense. The reformation of plaque deposits in arteries (restenosis) following angioplasty, however, is a major clinical problem encountered in as high as 40 percent of patients. Because reduction of health care costs is a major national priority, development of effective new preventative methods for restenoses is an important national priority.

Description:
Although the use of ionizing radiation for the treatment of benign lesions such as keloids has been available for nearly one hundred years, only recently have the cost effective benefits of such technology for the inhibition of arterial restenosis following controlled vessel damage from balloon angioplasty been fully realized. In particular, the use of balloons filled with solutions of beta-emitting radioisotopes for vessel irradiation provide the benefit of uniform vessel irradiation. Use of such contained ("unsealed") sources is expected to represent a new opportunity for nuclear medicine physicians working in conjunction with interventional cardiologists to provide this new approach for restenosis therapy.

Description:
Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.

Description:
The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective CHD risk was examined in healthy UK men. Of the 2808 men followed over nine years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [Hazard ratio (HR) of 2.07 (95%CI 1.04-4.12)] while men homozygous for APOC3 1100T were protected (HR 0.28 (95%CI 0.09-0.87)). In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using nine-SNP haplotype analysis, highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC31100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIVlevels, the relationship was examined in over 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.48 + 0.6mg/dl) compared to carriers of the T347 allele (14.85 + 0.12 mg/dl) (p=0.025). These results demonstrate that genetic variation in and around APOA4, independent of effects of TG, is associated with risk of CHD and apoAIV levels, supporting an anti-atherogenic role for apoAIV.

Description:
The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with synchrotron radiation at SSRL and NSLS have shown that such an intravenous angiography procedure would be possible with an intense source of monochromatic X-rays. Because of the high cost of an electron synchrotron, theoretical analysis and experiments using inanimate phantoms has been undertaken to demonstrate the feasibility of using the spectrum produced by two appropriately chosen anode materials when bombarded with electrons in the 100--500 keV energy range for angiography. By using the X-rays emitted at 120{degree} to the incident electron direction, about 20--30% of the X-ray intensity would be due to K-emission lines. Calculations using the TIGERP Monte Carlo Code, have shown that high quality angiograms of human coronary arteries should be possible with a contrast agent containing ytterbium, if an electron beam pulses of 16 kJ were used for each anode target. The experimental program supported in part by the DOE has consisted of these theoretical calculations and experiments at the Dynamitron Electron Accelerator Facility at BNL.

Description:
Ernest Orland Lawrence Berkeley National Laboratory (Berkeley Lab) is the oldest of America's national laboratories and has been a leader in science and engineering technology for more than 65 years, serving as a powerful resource to meet Us national needs. As a multi-program Department of Energy laboratory, Berkeley Lab is dedicated to performing leading edge research in the biological, physical, materials, chemical, energy, environmental and computing sciences. Ernest Orlando Lawrence, the Lab's founder and the first of its nine Nobel prize winners, invented the cyclotron, which led to a Golden Age of particle physics and revolutionary discoveries about the nature of the universe. To this day, the Lab remains a world center for accelerator and detector innovation and design. The Lab is the birthplace of nuclear medicine and the cradle of invention for medical imaging. In the field of heart disease, Lab researchers were the first to isolate lipoproteins and the first to determine that the ratio of high density to low density lipoproteins is a strong indicator of heart disease risk. The demise of the dinosaurs--the revelation that they had been killed off by a massive comet or asteroid that had slammed into the Earth--was a theory developed here. The invention of the chemical laser, the unlocking of the secrets of photosynthesis--this is a short preview of the legacy of this Laboratory.

Description:
There is overwhelming evidence that addiction is a disease of the brain (Leshner, 1997). Yet public perception that addiction is a reflection of moral weakness or a lack of willpower persists. The insidious consequence of this perception is that we lose sight of the fact that there are enormous medical consequences of addiction including the fact that a large fraction of the total deaths from cancer and heart disease are caused by smoking addiction. Ironically the medical school that educates physicians in addiction medicine and the cancer hospital that has a smoking cessation clinic are vanishingly rare and efforts at harm reduction are frequently met with a public indignation. Meanwhile the number of people addicted to substances is enormous and increasing particularly the addictions to cigarettes and alcohol. It is particularly tragic that addiction usually begins in adolescence and becomes a chronic relapsing problem and there are basically no completely effective treatments. Clearly we need to understand how drugs of abuse affect the brain and we need to be creative in using this information to develop effective treatments. Imaging technologies have played a major role in the conceptualization of addiction as a disease of the brain (Fowler et al., 1998a; Fowler et al., 1999a). New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology and medicine. This topic cuts across the medical specialties of neurology, psychiatry, cancer and heart disease because of the high medical, social and economic toll that drugs of abuse, including and especially the legal drugs, cigarettes and alcohol, take on society. In this chapter we will begin by highlighting the important role that chemistry has played in making it possible to quantitatively image the movement ...

Description:
Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells is thought to be most important. We show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese and even under extreme conditions, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analyzing the integration of {sup 14}C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in obesity, suggesting a tight regulation of fat cell number that is independent of metabolic profile in adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.

Description:
The project analyzed the challenges raised by complex genetic disorders in genetic counselling, for clinical practice, for public health, for quality assurance, and for protection against discrimination. The research found that, in some settings, solutions created in the context of single gene disorders are more difficult to apply to complex disorders. In other settings, the single gene solutions actually backfired and created additional problems when applied to complex genetic disorders. The literature of five common, complex genetic disorders--Alzheimer's, asthma, coronary heart disease, diabetes, and psychiatric illnesses--was evaluated in depth.

Description:
Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased ...

Description:
It is well known that the electrical signals generated by the heart exhibit nonlinear, chaotic dynamics. A number of heart pathologies alter heartbeat dynamics and/or the electrical properties of the heart, which, in turn, alter electrocardiogram signals. Electrocardiogram techniques in common use for diagnosing pathologies have limited sensitivity and specificity. This leads to a relatively high misdiagnosis rate for ventricular fibrillation. It is also known that the linear analysis tools utilized (such as fast Fourier transforms and linear statistics) are limited in their ability to find subtle changes or characteristic signatures in nonlinear chaotic electrocardiogram signals. In contrast, the authors` research indicates that chaotic time-series analysis tools that they have developed allow quantification of the nonlinear nature of dynamic systems in the form of nonlinear statistics, and also enable characteristic signatures to be identified. The goal of this project is to modify these tools to increase and enhance the medically useful information obtained from electrocardiogram signals through the application of chaotic time series analysis tools. In the one year of the project, the tools have been extended to enhance the capabilities for detecting ventricular fibrillation. Chaotic time-series analysis provides a means to increase sensitivity in detecting general heart dynamics. Oak Ridge National Laboratory specialists have worked with Physio-Control and their medical collaborators to extend the capabilities of state-of-the-art electrocardiogram systems and interpretation of results.

Description:
This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). This project has supported the collaborative development with Sandia National Laboratories (SNL) and the University of New Mexico (UNM) of two critical components for a hand-held low-field magnetic sensor based on superconducting quantum interference device (SQUID) sensor technology. The two components are a digital signal processing (DSP) algorithm for background noise rejection and a small hand-held dewar cooled by a cryocooler. A hand-held sensor has been designed and fabricated for detection of extremely weak magnetic fields in unshielded environments. The sensor is capable of measuring weak magnetic fields in unshielded environments and has multiple applications. We have chosen to pursue battlefield medicine as the highest probability near-term application because of stated needs of several agencies.

Description:
This booklet is one of a series of bilingual guides to environmental-science learning activities for students to do at home. Lesson objectives, materials required, procedure, vocabulary, and subjects integrated into the lesson are described in English. A bilingual glossary, alphabetized by English entries, with Spanish equivalents and definitions in both English and Spanish, follows the lesson descriptions, and is itself followed by a bibliography of English-language references. This booklet includes descriptions of ten lessons that cover the following topics: safe and unsafe conditions for chemical combinations; growth rates and environmental needs of plants; photosynthesis and effects of ozone-layer depletion; the circulatory system, the importance of exercise to the heart, and selected circulatory diseases; the nervous system; specific nutritional values of the different food groups; significance of including, reducing, or eliminating certain foods for a healthy diet; effects of some common chemicals on plant growth and animal life; plants` and animals` natural habitats; and dangers of non-biodegradable garbage.

Description:
Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.

Description:
This grant is to support a research in robotics at three major medical centers: the University of Southern California-USC- (Project 1); the University of Alabama at Birmingham-UAB-(Project 2); and the Cleveland Clinic Foundation-CCF-(Project 3). Project 1 is oriented toward cardiovascular applications, while projects 2 and 3 are oriented toward neurosurgical applications. The main objective of Project 1 is to develop an approach to assist patients in maintaining a constant level of stress while undergoing magnetic resonance imaging or spectroscopy. The specific project is to use handgrip to detect the changes in high energy phosphate metabolism between rest and stress. The high energy phosphates, ATP and phosphocreatine (PCr) are responsible for the energy of the heart muscle (myocardium) responsible for its contractile function. If the blood supply to the myocardium in insufficient to support metabolism and contractility during stress, the high energy phosphates, particularly PCr, will decrease in concentration. The high energy phosphates can be tracked using phosphorus-31 magnetic resonance spectroscopy ({sup 31}P MRS). In Project 2 the UAB Surgical Robotics project focuses on the use of virtual presence to assist with remote surgery and surgical training. The goal of this proposal was to assemble a pilot system for proof of concept. The pilot project was completed successfully and was judged to demonstrate that the concept of remote surgical assistance as applied to surgery and surgical training was feasible and warranted further development. The main objective of Project 3 is to develop a system to allow for the tele-robotic delivery of instrumentation during a functional neurosurgical procedure (Figure 3). Instrumentation such as micro-electrical recording probes or deep brain stimulation leads. Current methods for the delivery of these instruments involve the integration of linear actuators to stereotactic navigation systems. The control of these delivery devices utilizes an open-loop configuration involving a team ...

Description:
The XXIst International Conference on Magnetic Resonance in Biological Systems (ICMRBS 2005), '60th anniversary of the discovery of Nuclear Magnetic Resonance,' was held between 16 and 21 January 2005 in Hyderabad, India. The meeting focused on a broad range of magnetic resonance methods as applied to studies of biological processes related to human health. The biennial ICMRBS has become the major venue for discussion of advances in nuclear and electron magnetic resonance (NMR & EMR/EPR) studies of the structure, dynamics, and chemical properties of important classes of biomolecules. Magnetic resonance has become an established tool in structural biology, and its special importance derives from its ability to provide atomic level information. It is becoming increasingly evident that the dynamic features of biomolecules, their intermolecular interactions, and accessible conformations in solution are data of key importance in understanding molecular recognition and function. NMR, which is already contributing to approximately 25% of the new structures being deposited with the Protein Data Bank, is destined to be a major player in the post genomic structure age with its emphasis on structure and function. In-vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) results shed light on human metabolic processes and on the cellular ramifications of cancer, stroke, cardiovascular disease, and other pathologies. New methodologies in metabonomics may lead to development of new drugs and medical diagnosis. The ICMRBS is the one conference that brings together experts from high-resolution NMR, solid state NMR, EPR, in-vivo MRS and MRI, and developers of instrumentation, techniques, software, and databases. Symposia at this ICMRBS are designed to continue the fruitful cross-fertilization of ideas that has been so successful in driving the spectacular advances in this field. ICMRBS 2005 maintained the traditional format of poster sessions, and plenary lectures that highlight major advances in each of the major ...

Description:
From 11th international annual meeting of the German Society of Nuclear Medicine; Athens, Greece (24 Sep 1973). Rubidium-81 is a new myocardial imaging agent with an ideal T/sub 1/2 of 4.6 hr and energies acceptable for gamma-camera viewing. The target-to-nontarget ratio for heart image to background in the projection images is usually less than 2: 1, thus good statistics are necessary to delineate lesions. The low radiation dose and availability of this isotope allow one to obtain 6 to 10 times the data, and /sup 81/Rb is probably superior to /sup 129/Cs and /sup 43/K for myoca rdial imaging if adequate collimation is present. (auth)

Description:
An improved method for non-traumatic and essentially noninvasive evaluation of left ventricular (LV) function with /sup 99m/Tc as the tracer was developed. This method combines previously used EKG gating techniques for cardiac blood pool visualization with new computerized acquisition, processing and display techniques. An Anger camera, a small computer, and a physiological synchronizer are used to acquire a sequence of eight scintigrams which span the entire cardiac cycle. Under our present protocol two twenty-minute sequences are obtained, one an LAO (50$sup 0$) projection, the other an RAO (30$sup 0$) projection. Subsequently these images are processed on-line with a digital filter to increase definition of the cardiac borders. The eight images are then displayed sequentially on a specially designed electronic monitor to give an impression of the beating heart somewhat analogous to that obtained with invasive contrast angiography. (auth)

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